It is known that the expression of various cytokines and cell adhesion molecules is involved in inflammatory responses. Binding the inflammatory cytokines to their specific receptors induces many lines of phosphorylation cascade within the cell cytoplasm. It is considered that these lines of phosphorylation cascade ultimately converge into activation of NFκB, which is a nuclear transcription factor, to enhance the transcriptions for inflammatory materials in the cell.
Thus, the inflammatory responses ultimately converge into the activation of NFκB. A steroid agent is used as an agent that effectively inhibits this transcriptional activity of NFκB.
Steroid agents are used as effective drugs for the treatment of intractable autoimmune hepatitis, fulminant hepatic failure and chronic hepatitis as well as liver cirrhosis and liver cancer induced by them. However, it is known that while steroid agents have a very potent effect, they also have serious side effects such as steroid ulcer, moon face, diabetes or osteoporosis. These side effects are in many cases caused in accordance with the amount used thereof. Further, the steroid agents are known to exhibit various effects on cell proliferation or sugar metabolism, other than the anti-inflammatory effect. The details of the anti-inflammatory effect of the steroid agent have not yet been completely elucidated.
On the other hand, it is known that NFκB is involved in the onset of various diseases including auto-immune diseases such as rheumatism and collagen diseases and allergy diseases such as asthma and pollen allergy, and not only with inflammatory diseases (acute and chronic hepatitis, kidney inflammation, articular inflammation and the like). Therefore, it is predicted that the inhibition of the transcriptional activity of NFκB could relieve the symptoms related to the NFκB.
Therefore, as an agent alternative to steroid agents, or as various therapeutic agents, development of a substance that inhibits the transcriptional activity of NFκB has progressed with a focus on natural extracts and synthetic substances (for example, Patent documents 1 to 3).
Further, in Patent document 4, the focus is placed particularly on p65 subunit of NFκB. Inhibiting the transcriptional activity of NFκB by using an RelA binding inhibitor that binds to this p65 subunit is described. Patent document 1: JP-A-8-319238    Patent document 2: JP-A-9-59151    Patent document 3: JP-A-11-279057    Patent document 4: JP-A-2000-224993